Reticuloendothelial system (RES) function was assessed following surgery, trauma, and other forms of injury. Emphasis was placed on the serum level of an opsonic protein which mediates the phagocytic activity. The opsonic protein from human serum was isolated. It is a large molecular weight alpha-w-glycoprotein which is identical to cold-insoluble globulin (CIg) or plasma fibronectin. An immunoassay for measurement of this protein in patients has been developed. Depletion of this protein following trauma and shock has been confirmed by immunoassay. Reticuloendothelial phagocytic depression following trauma impairs the hepatic clearance of blood-borne altered platelets, fibrin aggregates, and fibrin monomer, and test colloids and is associated with an increased pulmonary localization of such blood-borne test particulates. Intravascular coagulation or RE blockage did not initiate pulmonary disruption but intravascular coagulation in the presence of maintained RE depression initiates alterations in pulmonary hemodynamics and gas exchange. Septic surgical, burn, and trauma patients demonstrate bioassayable and immunoreactive opsonic deficiency coupled with multiple organ failure, especially pulmonary insufficiency. Administration of opsonic protein by cryoprecipitate (CIg rich) therapy to patients with documented opsonic deficiency restored opsonic activity and was associated with an improvement in their clinical course as evaluated by febrile and septic state, leukocyte levels, and pulmonary function. These studies suggest that immunoreactive serum opsonic alpha-2-SB-glycoprotein may provide a non-invasive index of reticuloendothelial function and opsonin therapy may have potential in the treatment of the surgical, burn or trauma patient.